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Title: Glutathione, the redox sensitive transcription factors AP-1 and NF-κB, and early one adenoviral protein in human lung in smoking related lung disease
Author: Crowther, Ann Jeannette Louise
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2007
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NF-κB and AP-1 are both redox sensitive transcription factors, and are involved in the regulation of the gene transcription of many pro-inflammatory mediators.  AP-1 and NF-κB have a close relationship with γ-glutamylcysteine synthetase (γ-GCS), the rate limiting enzyme in the synthesis of glutathione, with the γ-GCS gene containing various elements including an AP-1 binding site. Susceptibility to the effects of cigarette smoke is likely to explain why certain individuals develop COP and this susceptibility may arise from an earlier viral infection such as adenoviral infection that lies dormant, but which in the face of an oxidant stimulus such as cigarette smoke augments the inflammatory process. The in vivo studies herein have examined glutathione and γ-GCS gene transcription, oxidant/antioxidant imbalance, the redox sensitive transcription factors NF-κB and AP-1 and have assessed for the presence of the early one adenoviral protein in human lung in smokers and patients with COPD. The results how similar levels of total GSH in the lungs of patients with and without airflow obstruction, and decreased γ-GCS activity in patients with severe airflow obstruction who have undergone LVRS for emphysema compared to those with no airflow obstruction. Local lung oxidative stress as measured by malondialdehyde, and TEAC a marker of systemic oxidative stress did not correlate with lung function. DNA binding of NF-κB correlated with lung function as measured by percent predicted FEV1, however no such relationship was found with AP-1 DNA binding. Examination for EIA gene and protein in lung tissue failed to reveal conclusive results.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available